This is a request for continued funding for unique study of adoptive and non-adoptive families, the Sibling Interaction and Behavior Study (SIBS). The major aim of SIBS is to investigate the origins of adolescent alcohol use and abuse and associated behavioral pathology within a developmental biopsychosocial framework. In the initial period of funding, we systematically ascertained and assessed 409 adoptive and 208 non-adoptive families, each consisting of a pair of adolescent siblings and their rearing parents. Families completed an extensive 5-hour, in-person assessment that included measurement of substance use and abuse, mental health, family and social environment, and individual-level markers of risk. In this continuation application, we seek to complete analysis of the intake SIBS dataset and explore the interplay of genetic and environmental influences on adolescent development. In completing the analysis of the intake SIBS dataset, we will test the following hypotheses: 1) shared environmental influences exert a consistent effect on adolescent disinhibitory psychopathology, including adolescent alcohol use, and 2) siblings, rather than parents, are the major source of shared environmental influence on adolescent disinhibitory behavior. To investigate gene-environment interplay, SIBS participants will be genotyped on 8-12 candidate genes selected as being relevant to vulnerability to disinhibitory psychopathology. Our sample of adopted adolescents includes a sizable number of East Asians, who will also be genotyped on the ALDH2 polymorphism. Analysis of the ALDH2 data will focus not only on whether it is protective against alcohol consumption in East Asians reared in non-East Asian homes, but also on the factors that account for heavy alcohol consumption among East Asian adolescents who inherit ALDH2 deficiency. In the analysis of the ALDH2 data, we will also make use of the principles of Mendelian randomization to test the hypothesis that reducing adolescent drinking also results in reductions in other problem behaviors. [unreadable] [unreadable] [unreadable] [unreadable]